Molecular Neurobiology

, Volume 53, Issue 9, pp 5847–5863 | Cite as

Dehydroascorbic Acid Promotes Cell Death in Neurons Under Oxidative Stress: a Protective Role for Astrocytes

  • Andrea García-Krauss
  • Luciano Ferrada
  • Allisson Astuya
  • Katterine Salazar
  • Pedro Cisternas
  • Fernando Martínez
  • Eder Ramírez
  • Francisco Nualart


Ascorbic acid (AA), the reduced form of vitamin C, is incorporated into neurons via the sodium ascorbate co-transporter SVCT2. However, this transporter is not expressed in astrocytes, which take up the oxidized form of vitamin C, dehydroascorbic acid (DHA), via the facilitative hexose transporter GLUT1. Therefore, neuron and astrocyte interactions are thought to mediate vitamin C recycling in the nervous system. Although astrocytes are essential for the antioxidant defense of neurons under oxidative stress, a condition in which a large amount of ROS is generated that may favor the extracellular oxidation of AA and the subsequent neuronal uptake of DHA via GLUT3, potentially increasing oxidative stress in neurons. This study analyzed the effects of oxidative stress and DHA uptake on neuronal cell death in vitro. Different analyses revealed the presence of the DHA transporters GLUT1 and GLUT3 in Neuro2a and HN33.11 cells and in cortical neurons. Kinetic analyses confirmed that all cells analyzed in this study possess functional GLUTs that take up 2-deoxyglucose and DHA. Thus, DHA promotes the death of stressed neuronal cells, which is reversed by incubating the cells with cytochalasin B, an inhibitor of DHA uptake by GLUT1 and GLUT3. Additionally, the presence of glial cells (U87 and astrocytes), which promote DHA recycling, reverses the observed cell death of stressed neurons. Taken together, these results indicate that DHA promotes the death of stressed neurons and that astrocytes are essential for the antioxidative defense of neurons. Thus, the astrocyte-neuron interaction may function as an essential mechanism for vitamin C recycling, participating in the antioxidative defense of the brain.


Ascorbic acid Dehydroascorbic acid Neuron Astrocyte Cell death Recycling Oxidative stress 



Ascorbic acid


Dehydroascorbic acid


Dulbecco’s modified Eagle’s medium


Fetal bovine serum




Glial fibrillary acidic protein


Glucose transporter




Iscove’s modified Dulbecco’s medium


Polyacrylamide gel electrophoresis


Phosphate-buffered saline


Reactive oxygen species


Sodium dodecyl sulfate



This work was supported by a grant from the Fondo Nacional de Ciencia y Tecnología (FONDECYT 1140477) to FN and Conicyt PIA ECM12. We thank Dr. Marjet Heitzer for critical reading and editing of the manuscript and Ms. Ximena Koch for technical support.

Compliance with Ethical Standards

All animals were handled in strict accordance with the Animal Welfare Assurance (permit number: 2010101A), and all animal work was approved by the Ethics and Animal Care and Use Committee of the University of Concepcion, Chile. Female adult Sprague–Dawley rats were used for the experiments and were kept under a 12-h light/dark cycle with food and water provided ad libitum.

Conflict of Interest

The authors declare that they have no competing interests.


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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Andrea García-Krauss
    • 1
  • Luciano Ferrada
    • 1
  • Allisson Astuya
    • 1
  • Katterine Salazar
    • 1
  • Pedro Cisternas
    • 1
  • Fernando Martínez
    • 1
  • Eder Ramírez
    • 1
  • Francisco Nualart
    • 1
    • 2
  1. 1.Center for Advanced Microscopy (CMA) BIO-BIO, Faculty of Biological SciencesConcepcion UniversityConcepciónChile
  2. 2.Departamento de Biología Celular, Facultad de Ciencias BiológicasUniversidad de ConcepciónConcepciónChile

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